IC16 Hypertension in Pregnancy + Contraception Flashcards
What are the BP cuts off for hypertension in pregnancy and when to start treatment?
BP cut offs:
- HTN: >140/90 mmHg (2 measurements, at least 4 hr apart) –> START TREATING*
- Severe HTN: >160/110mm Hg (2 measurements)
What are the 4 different types of hypertension in pregnancy?
Chronic HTN
* Pre-existing HTN / new onset HTN before 20wks gestation
Gestational HTN
* New onset HTN after 20wks gestation
* No proteinuria
Pre-eclampsia
* New onset HTN after 20wks gestation
* New onset of Proteinuria / end organ dysfunction / uteroplacental dysfunction after 20wks
Chronic HTN with superimposed pre-eclampsia
* New onset proteinuria before 20wks gestation
* Chronic HTN (pre-existing)
What are some test / labs to look at to see whether the patient has pre-eclampsia?
What are the severe symptoms of eclampsia?
Pre-eclampsia:
- Test for Proteinuria:
a. 24hr urinary protein > 300mg
b. Dipstick protein >= 2+
c. Urine protein:creatinine ratio > 0.3 mg/dL - Test for end organ damage
a. Low platelet count –> liver damage
b. LFT > 2x ULN
c. Doubling of SCr in the absence of other renal disease
d. Pulmonary edema
e. Neurologic complications – onset of headaches, visual disturbances, seizures
Rapidly progress to eclampsia
* tonic-clonic, focal, multifocal seizures superimposed on preeclampsia
* medical emergency
how to prevent pre-eclampsia? In which patient groups?
Prevention of Pre-eclampsia:
Low dose aspirin 100mg or 150mg daily
- give to high-risk patients e.g.
o HTN in previous pregnancy
o multifetal gestation (twins/triplets)
o autoimmune disease
o DM
o CKD
o lupus nephritis - start after 12 weeks of gestation (after 1st trimester) and before 16 weeks, continue till delivery
- hypothesize MOA: helps to increase uteroplacental blood flow by inhibiting thromboxane A2
What are the possible treatment options for hypertension in pregnancy?
Medication
- Methyldopa
* Huge amt of evidence on safety
* Rarely used due to low potency + increase ADR (sedation, dizziness) - Labetalol
* Commonly used
* Lower adverse effects on uteroplacental blood flow and fetal growth than beta blockers
* ADR: bronchoconstriction (avoid in asthma/COPD), bradycardia
* Alpha + beta blocker - Nifedipine ER
* Commonly used
* ADR: pedal edema, flushing, headache - Hydrochlorothiazide
* 2nd /3rd line
* Interferes with normal blood volume expansion in pregnancy (since it is a diuretic which reduces blood volume) - Hydralazine
* Rarely used
* ADR mimics symptoms of severe pre-eclampsia + imminent eclampsia: N&V, palpitation, flushing, headache, tremor
Avoid ACEi / ARBs in pregnancy
What are the 2 main MOA of contraception?
2 Main MOA:
- Prevent fertilization – Prevent sperm from coming into contact with mature ovum / Prevent ovulation
- Prevent implantation of fertilized eggs on to the endometrium
What are the barrier methods, their CI, Pros and cons? What is the failure rate?
Barrier Techniques Contraindications Pros Cons
- External Condom (male)
Contraindication:
Allergy to material (latex/rubber)
Pros:
STD protection
Cons:
High failure rate
Poor acceptance
Possibility of Breakage
- Internal Condom (female)
CI:
Allergy to material (polyurethane)
History of toxic shock syndrome (TSS)
Pros:
STD protection
Inserted ahead of time
Cons:
High failure rate
Uncomfortable with ring hanging outside
- Diaphragm with spermicides and Cervical Cap
CI:
Allergy to material (latex/rubber/spermicide)
Recurrent UTIs
History of TSS
Abnormal gynecological anatomy
Pros:
Reusable
Low cost
Cons:
High failure rate
Low STD protection
Increase risk of UTI
Cervical irritation
- Failure rate / rate of pregnancy 13-21%
What are examples of estrogen?
What are the MOA of estrogen?
What is the high dose estrogen?
When to use high dose?
Estrogen
- MOA:
suppress FSH release, prevent ovulation
mainly stabilize endometrial lining & provide cycle control - Examples: Ethinyl estradiol, Estradiol valerate, Esterol, Mestranol
- Low dose: 20-25 mcg (default)
- High dose: 30-35mcg
Obesity / weight > 70.5kg
Early / mid cycle breakthrough bleeding or spotting (mimic normal cycle)
Non-adherent
What are examples of progestrerone?
What are the MOA of progestrerone?
When to use high dose?
Progestin
- MOA:
thickens cervical mucous prevent sperm penetration, slowing tubal motility (delay sperm transport), induce endometrial atrophy
blocks LH surge, prevent ovulation
provides most of the contraceptive effects - Variable activity and androgenic effects
- Examples:
(1st gen) norethindrone, ethynodiol diacetate, norgestrel, norethindrone acetate
(2nd gen) levonorgestrel
(3rd gen) norgestimate, desogestrel
(4th gen) Drospirenone - MOA: mild diuretic similar to spironolactone, anti-androgenic, cause less water retention, less acne
- ADR: hyperkalemia, thromboembolism, bone loss
(4th gen) Cyproterone - MOA: anti-androgenic, antigonadotrophic, primary indication: severe acne, hirsutism
- should not be use alone for contraception
- ADR: thromboembolism
o Higher dose:
Late cycle breakthrough bleeding
Painful menstrual cramps
How to categorize COC? What are the pros and cons of each type of COC?
Relative Amount
Monophasic
Definition:
Same amount of estrogen and progesterone in every pill
Pros:
- Less confusing
- Convenient (simpler missed dose)
Multiphasic:
Variable amount of estrogen and progesterone for different pills
(usually, more E in front and more P at the end of cycle)
Pros:
- Less progestins –> less ADR
Duration:
Conventional / New formulation
Definition Conventional:
21 days (pills) + 7 days (placebo)
New formulation:
24 days (pill) + 4 days (placebo)
Pros & Cons Conventional: Mimic normal cycle
New formulation: Reduce hormonal fluctuations –> less ADR
Extended / Continuous
Extended:
84 days (pills) + 7 days (placebo)
Continuous:
no placebo
Pros:
- Convenient (Lesser periods)
Cons:
- may have breakthrough bleeding
What are the different initiation methods for COC?
- First Day:
Start on 1st day of menstrual cycle
No need back up contraceptive required
(Since they have 5-6 pills once period ends)
Simplest method
Mimic normal Cycle - Sunday Start:
Start on the 1st Sunday after menstrual cycle begins
Need back up contraceptive for at least 7 days
(Need to rely on other methods such as barrier technique / abstinence)
Ensures that menstrual does not occur on weekends
(the 22nd day after 21 days of pills will be a Sunday, and ideally the next day or Tuesday will be the start of the next cycle)
- Quick Start:
Start now
Need back up contraceptive for at least 7 days & potentially until the next menstrual cycle begins
(Need to rely on other methods such as barrier technique / abstinence)
Convenient if need to start asap
What are some considerations when choosing COC?
Considerations in choosing COC:
- Hormonal content required
* Higher dose estrogen for obese or weight > 70.5kg, non-adherent, early or mid-cycle breakthrough bleeding - Convenience
* (adherence/administration) Monophasic –> since less complicating, no need to worry which pill to take for different days + missed dose instructions are simpler
* (Want less menses) extended or continuous COC –> 1 period in 3 months or no period at all - Tendency for oily skin, acne, hirsutism (androgenic issues)
* Avoid giving progestins with androgenic effects
* Give alternatives e.g. drospirenone, cyproterone - Medical conditions
* Dysmenorrhea, cramping give more progestins / extended / continuous COC / new formulations
* PMS, PCOS etc.
What are the benefits of using COC?
Benefits:
- Prevent pregnancy
- Improve menstrual irregularity (conventional / new formulation)
- Relief menstrual related issues e.g. cause amenorrhea (specifically continuous regime), dysmenorrhea, menorrhagia
- Antiandrogenic effects (specifically progestins drospirenone, cyproterone)
- Improve perimenopause
- Efficacious against polycystic ovarian syndrome (PCOS), premenstrual syndrome (PMS), premenstrual dysphoria disorder (PMDD)
- Iron-deficient anaemia (progestins since it can lead to amenorrhea)
- Reduce risk of ovarian and endometrial cancers
- Reduce risk of ovarian cysts, ectopic pregnancy (fertilized egg implants outside of uterus), pelvic inflammatory diseases, endometriosis, uterine fibroids, benign breast disease
What are the possible CI for COC?
Contraindications:
- Breast Cancer
- Venous thromboembolism / DVT / PE
- Ischaemic stroke / Myocardial infarction
- Immobilization after major surgery
- <21 days of postpartum
- Thrombogenic mutations
- Migraine with auras
- BP > 160/100 mmHg
- HTN with vascular disease
- Ischemic heart disease
- Cardiomyopathy
- Smoking >= 15 sticks/day AND >= 35 y/o
- History of cerebrovascular disease
Which component of COC increases a person’s risk to breast cancer?
When to avoid COC due to risk of breast cancer?
Breast Cancer
- Caused by COC (both estrogen and progesterone components)
- Risk factor: long duration use, >40 y/o
- Avoid in
women > 40y/o,
family history of breast cancer,
PMH or current breast cancer (within 5 years) - Risk reduces to normal when discontinue
Which component of COC increases risk of VTE?
What are the risk factors of VTE?
What to do for these people with the risk factors?
Venous thromboembolism / DVT / PE
- Mainly caused by estrogen
- MOA: increase hepatic production of factor VII, factor X, fibrinogen of coagulation cascade
- Possibly by new generation progestins e.g. drospirenone, cyproterone, desogestrel –> unknown
- Risk factor:
>35 y/o,
obese,
immobility e.g. due to surgery,
smoking,
family history of VTE,
cancer
o Risk in COC users is not as high as that in pregnancy
o Use low dose estrogen & old progestins / switch to POP / barrier methods
Which component of COC increases the risk of MI / stroke?
What are the risk factors of MI and stroke?
What can be done for them?
Ischaemic stroke / Myocardial infarction
- Linked to VTE
- Mainly caused by estrogen
- Risk factors:
age,
HTN,
migraine with aura,
obesity,
dyslipidemia,
smoking and
prothrombotic mutations - Absolute contraindication w all COC – migraine with aura (1 sided pain with sensory disturbances) –> use POP or barrier methods
- Other risk factors –> use low dose estrogen in COC, POP or barrier methods
What are the SE of using COC and how to overcome them?
Side effects:
Usually occur in the first 3-4 cycle of COC use –> thus, try to persevere for the 1st 2-3 months before changing product unless severe side effects e.g. VTE, stroke, migraine with aura, MI etc.
Side Effects & Alternatives:
- Breakthrough bleeding
If early / mid cycle – increase estrogen
If late – increase progestin - Acne
(usually due to progestin)
Give anti-androgenic progestins e.g. drospirenone, cyproterone /
Increase estrogen /
If on POP, change to COC - Bloating
(usually due to estrogen)
Reduce estrogen /
Use drospirenone (similar spironolactone have diuretic effects) - N&V
(usually due to estrogen)
Reduce estrogen /
Take pill at night /
Use POP - Headache
(usually occur during placebo)
Exclude migraine with aura
Use extended / continuous / new formulation - Menstrual cramps
Increase progestins /
Use POP / extended / continuous - Breast tenderness / weight gain
Keep both estrogen and progestin as low as possible
What are the DDI of COC?
Drug interactions:
Drugs Effects + Management
- Rifampin
Since both estrogen and progesterone are metabolized by gut flora into active drug, antibiotics can reduce metabolism of COC and reduce free serum concentration
Rifampicin shows significant interactions out of all other antibiotics
- use additional contraception till rifampicin discontinued for at least 7 days
(so means e.g. 6 months + 1 week of additional contraceptive)
- Anticonvulsants
Reduce free serum concentration of both estrogen and progesterone
E.g. Phenytoin, carbamazepine, barbiturates, topiramate, oxcarbazepine, lamotrigine
- increase dose
- HIV antiretrovirals
Reduce both effectiveness of COC and antiretrovirals
E.g. ritonavir, darunavir (protease inhibitor)
What to do for miss dose for COC?
Miss 1-2 dose (<48 hours)
- Take missed dose immediately & continue the rest as usual
(Thus, might take 2 pills in a day) - No need additional contraceptive methods
Miss 2 or more doses (>48 hours) – Early
- Take 1 missed dose immediately
(Thus, might take 2 doses in a day)
& discard the rest of the missed dose
& continue the rest as usual - Need back up contraceptive methods of at least 7 days
Miss 2 or more doses (>48 hours) – Late, last week of cycle e.g. 15-21 days
- Finish the rest of the pills for that cycle
& skip the placebo / pill free interval
& start the new cycle immediately on the next day after finishing the previous cycle
(treat the missed days as “period”) - Need back up contraceptive methods of at least 7 days
What are the benefits of POP? / When do you use POP?
What is the failure rate?
What is the CI?
What is the duration of treatment for POP?
How to initiate?
What to do if missed dose?
Progestin only pills (The Minipill)
Benefits:
- prevent pregnancy,
- good for breast feeding,
- intolerant to estrogen e.g. N&V,
- medical conditions that preclude estrogen, amenorrhea, reduce cramps
Failure rate: 7% = COC
CI: breast cancer
Duration: continuous for 28 days of active pills
Initiate:
* within 5 days of menstrual cycle –> no back up needed
* any other day –> back up contraceptive of 2 days
Missed dose:
* >3 hours: need back up contraceptive of 2 days
What are the transdermal patch and vaginal ring?
What are the pros and cons of transdermal patch and vaginal ring?
- Transdermal patch
(Estrogen & Progestin)
Once weekly for 3 weeks + 1 patch free week
Failure rate 7% = COC
Not effective in pts > 90kg
ADR: similar to COC, application site reaction,
high risk VTE
- Vaginal Rings
(Estrogen & Progestin)
Use for 3 weeks then discard
Failure rate 7% = COC
No need to precisely place it
ADR: similar to COC,
tissue irritation,
risk of expulsion,
high risk VTE
(due to continuous higher exposure to estrogen)
What is the progestin injection?
What is the failure rate of progestin injections?
What are the pros and cons of progestin injections?
Progestins injections:
IM injection every 12 weeks (3 months)
Pros:
- Good adherence but need regular Dr visit
- Good for postpartum
Failure rate 4% < COC
Cons:
- Return to fertility might be delayed
- ADR: Variable breakthrough bleeding esp 1st 9 months, amenorrhea, weight gain,
- bone loss (reduce bone mineral density)
–> avoid in – older women, osteoporosis risk factor(use steroids), use for > 2yrs
What is LARC?
What is the MOA?
What is the failure rate?
What are the pros and cons?
Intrauterine device (IUD) [Long-acting reversible contraceptive (LARC)]
MOA:
- inhibit sperm migration, damage ovum, damage transport of fertilized ovum
If with progestin, endometrial suppression, thicken mucus
Pros:
- Failure rate 1% (perfect use)
- Quickly reversible upon removal
Cons:
- Invasive
- Avoid in – pregnant, current STI, undiagnosed vaginal bleeding, malignancy of genital tract, uterine anomalies, uterine fibroids
- Adverse effects: uterine perforation, expulsion, pelvic infection
What are the pros and cons of levonorgestrel and copper IUD?
Levonorgestrel IUD:
Pros:
- Good for menorrhagia since it causes amenorrhea
- Last 5 yrs
Cons:
- Spotting, amenorrhea
Copper IUD:
Pros:
- Good for amenorrhea since it causes heavy bleeding
- Can be used for emergency contraception
- Last 10yrs
Cons:
- Heavy bleeding
What is subdermal progestin implant?
What is the failure rate?
What are the pros and cons?
Subdermal progestin implant
[Long-acting reversible contraceptive (LARC)]
Failure rate 1% (perfect use)
Pros:
- Quickly reversible upon removal
- Last for 3 years
Cons:
- Invasive
- Adverse effects: irregular bleeding patterns with continued use e.g. amenorrhea, prolonged bleeding, spotting, frequent bleeding
